Enzymatic Biodegradation of Hydrogels for Protein
Delivery Targeted to the Small Intestine

Multiresponsive
poly­(methacrylic acid-<i>co</i>-<i>N</i>-vinylpyrrolidone)
hydrogels were synthesized with biodegradable
oligopeptide crosslinks. The oligopeptide crosslinks were incorporated
using EDC-NHS zero-length links between the carboxylic acid groups
of the polymer and free primary amines on the peptide. The reaction
of the peptide was confirmed by primary amine assay and IR spectroscopy.
The microgels exhibited pH-responsive swelling as well as enzyme-catalyzed
degradation targeted by trypsin present in the small intestine, as
demonstrated upon incubation with gastrointestinal fluids from rats.
Relative turbidity was used to evaluate enzyme-catalyzed degradation
as a function of time, and initial trypsin concentration controlled
both the degradation mechanism as well as the extent of degradation.
Trypsin activity was effectively extinguished by incubation at 70
°C, and both the microgels and degradation products posed no
cytotoxic effect toward two different cell lines. The microgels demonstrated
pH-dependent loading of the protein insulin for oral delivery to the
small intestine.